Objective:To provide a basis for improving the design and implementation of policies for ensuring the supply of pediatric drugs in China.Method:Based on the perspective of pharmaceutical enterprises,reviewed literature and conducts questionnaire surveys to identify the constraints in the development of pediatrict drugs throughout the entire drug lifecycle,and analyzes the constraints'concentration and urgency.Result:The main constraints include:difficulty in conducting clinical trials for children;the current registration and approval rules lack consideration for the specificity of pediatric drugs and specific requirements for application materials;lack of implementation rules and measures in the implementation process of incentive policies for pediatric drug production;The market interest mechanism of pediatric drugs is not yet perfect.Among them,research and development and payment for use are currently relatively concentrated issues.Discussion and suggestions:It is recommended that China fully utilize existing clinical trial data of pediatric and broaden sources,take multiple measures to increase investment in pediatric drug R&D;Develop special guidelines for pediatric drug application and encourage adult drug registration to submit pediatric research plans;Explore the optimization path of pediatrict drug production and supply based on typical cases;Provide more space for pediatric drugs in the rules of drug use and payment.

Objective:To analyze the risk factors of internalizing problems in adolescents aged 12 to 18 years,and provide supporting evidence for the scientific prevention and effective control of internalizing problems in adolescents.Methods:By systematically searching the Chinese and English databases such as CNKI,VIP,Wan-fang,PubMed,Web of Science,Psychology and Behavioral Sciences Collection,PsycInfo,PsycArticles and ERIC,literature on risk factors of internalizing problems among adolescents in the past 22 years was collected,and non-clinical literature using CBCL or YSR or TRF scales to measure related internalizing problems were included.Meta analysis was performed using CMA3.0,with r as the effect size indicator and random effects model combined with the effect size of risk factors.Results:Finally,77 and 18 risk factors literatures were included,including 7 risk fac-tors of individuals,7 risk factors of family,and 4 risk factors of school/community.The average correlation between family risk factors and internalizing problems of adolescents was the highest.Among family risk factors,parent-child attachment had the highest correlation.Conclusion:Individual risk factors,family risk factors and school/com-munity risk factors are significantly positively correlated with adolescent internalizing problems,and family risk fac-tors(especially parent-child attachment quality)have the highest correlation with adolescent internalizing problems.

Objective:To evaluate the diagnostic performance of radiomics model based on contrast-enhanced ultrasound(CEUS) in predicting pathological complete response(pCR) after neoadjuvant chemoradiotherapy(nCRT) in patients with locally advanced rectal cancer(LARC).Methods:One hundred and six patients with LARC who underwent total mesorectal excision after nCRT between April 2018 and April 2023 in the First Affiliated Hospital of Guangxi Medical University were retrospectively included, the patients were randomly divided into a training set of 63(14 pCR patients) and a validation set of 43(12 pCR patients) in a 6∶4 ratios. Radiomics features were extracted from the tumors′ region of interest of CEUS images based on PyRadiomics. Intra-class correlation coefficient(ICC), Mann-Whitney U test, and least absolute shrinkage and selection operator(LASSO) algorithms were used to reduce features dimension. Finally, 7 radiomics features relevanted to pCR were selected to construct an ultrasomics model using elastic network regression, based on the R language. A combined model was constructed by jointing clinical feature. The performance of the models was assessed with the area under the ROC curve(AUC). Results:The AUC of the ultrasomics model and the combined model was 0.695(95% CI=0.532-0.859) and 0.726(95% CI=0.584-0.868) respectively in the training set. The AUC of the ultrasomics model and the combined model was 0.763(95% CI=0.625-0.902) and 0.790(95% CI=0.653-0.928) respectively in the validation set. Both univariate and multivariate Logistic regression analyses showed that CA199( P<0.05) and ultrasomics score( P<0.001) could be an independent predictor of pCR after nCRT in patients with LARC. Conclusions:The CEUS-based radiomics scores has certain predictive value for whether LARC patients achieve pCR after nCRT, and may provide a non-invasive imaging biomarker for predicting LARC patients achieve pCR after nCRT.

ObjectiveTo investigate the antidepressant effect of Sinisan （SNS） by regulating glycogen aynthase kinase-3β （GSK-3β）/tumor necrosis factor alpha-induced protein 3（A20）/CCAAT enhancer binding protein β（C/EBPβ） to inhibit the activation of microglia. MethodA total of 72 male C57/6J mice were randomly divided into the normal group， model group， fluoxetine group （5.0 mg·kg^-1）， low-dose Sinisan group （4.9 g·kg^-1）， medium-dose Sinisan group （9.8 g·kg^-1）， and high-dose Sinisan group （19.6 g·kg^-1）， with 12 mice in each group. After one week of adaptive feeding， chronic unpredictable mild stress （CUMS） was performed to establish the depression model. In the fifth week， drug treatment was conducted for four weeks. In the ninth week， behavioral tests were performed， including sucrose preference test （SPT）， open field test （OPT）， elevated plus maze （EPM） test， and forced swimming test （FST）. Western blot was used to detect the expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， nitric oxide synthase （iNOS）， GSK-3β， A20， and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 （Iba1） and cluster of differentiation 68 （CD68） in microglia was detected by immunofluorescence. ResultAfter eight weeks of CUMS， compared with the normal group， the mice in the model group had a significantly reduced sucrose preference rate （P<0.01）， and the activity in the central area of the OPT was significantly reduced （P<0.01）. The activity in the open arm area of the EPM test was significantly reduced （P<0.05）， and the immobility time of FST was increased （P<0.01）. The expression levels of inflammatory proteins IL-1β， IL-6， and iNOS were increased （P<0.01）， and the fluorescence co-localization index of Iba1 and CD68 was increased （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ were significantly increased （P<0.05， P<0.01）. After four weeks of SNS intervention， compared with the model group， the mice in the SNS group had significantly increased sucrose preference rate （P<0.01）， significantly increased activities in the central area and the open arm area in the OPT and the EPM test （P<0.05）， and significantly reduced immobility time in the FST （P< 0.01）. The protein expression levels of IL-1β， IL-6， and iNOS were significantly decreased （P<0.05）， and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased （P<0.01）， and that of A20 was significantly increased （P<0.01）. ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.

Wuhutang is the 51st Chinese medicine prescription of Han ethnic group on in the catalogue of ancient classical prescriptions （the second batch） ，which originated from Renzhai' Straight Diections Prescriptions （《仁斋直指方》） by YANG Shiying in the Song dynasty，it is composed of 5 medicines， including Ephedrae Herba，Armeniacae Semen Amarum， Glycyrrhizae Radix et Rhizoma， tea and Gypsum Fibrosum. It treats shortness of breath and phlegm. Following the principle of textual research on the key information of ancient classical famous prescriptions， the author collected and recorded the ancient books of traditional Chinese medicine of Wuhutang with the method of Bibliometrics， and screened out 53 valid data， involving 41 ancient books. Based on the historical evolution， drug composition， main treatment of disease and syndrome， drug dosage， method of preparation and usage， drug origin and processing， the author conducted a dig and a systematic study of Wuhutang. The results show that：in the later generations， besides inheriting the original prescription， the composition of medicine was added or subtracted， and the frequency of addition of Mori Cortex was the most；in the treatment of disease and syndrome， most of them inherited the original prescription mainly treating asthma syndrome， also see in the treatment of asthma， cough and other lung disease， in the drug dosage and method of use ， it is suggested to inherit the original prescription， the dosage of each medicine is： Ephedrae Herba 2.89 g， Armeniacae Semen Amarum 4.13 g， Glycyrrhizae Radix et Rhizoma 1.65 g， tea 3.30 g， Gypsum Fibrosum 6.20 g， decoction， take warm clothes before eating；on the source of medcine，ephedra is made from the dried herbaceous stems of Ephedra sinica （Ephedraceae），bitter almond is made from the dried and mature seeds of Prunus armeniaca （Rosaceae），Licorice is made from the dried roots and rhizomes of Glycyrrhiza uralensis（Legumes）， tea is made from the buds leaves of Camellia sinensis（Camellia），plaster is made from Gypsum Fibrosum of sulfate mineral gypsum family. At the same time， we collected and sorted the modern clinical application literature of Wuhutang， and obtained 73 effective literatures， all of which are for the treatment of respiratory system diseases， especially for children's pneumonia and asthma， and mostly belong to"phlegm-heat obstructing the lung syndrome". Through the analysis and study of ancient books and modern applied literature， the historical evolution and prescription evolution of Wuhutang are clarified， and its key information is determined， in order to provide more accurate reference for the research and development of the classic Wuhutang and the rational addition and subtraction of the application.

OBJECTIVE To evaluate the medication adherence of patients with hypertension in medication consultation clinics， and to analyze its influencing factors. METHODS The data of 389 patients who visited the medication consultation clinics of our hospital from June 2021 to June 2023 were collected. Univariate and multivariate Logistic regression analysis were used to analyze the related factors affecting medication adherence of hypertensive patients or those receiving different types of drugs. RESULTS Among 389 patients with hypertension， 302 cases （77.63%） had good adherence. Multivariate Logistic analysis showed that higher education level [corrected OR＝2.25， 95%CI （1.29， 3.93）， P＝0.004] was positively correlated with medication adherence， average blood pressure level [corrected OR＝0.19， 95%CI （0.10， 0.37）， P＜0.001]， without complication [corrected OR＝0.47， 95%CI（0.26，0.84），P＝0.010] and antihypertensive drug regimen being free dose combination [corrected OR＝0.27，95%CI（0.15， 0.47）， P＜0.001] were negatively correlated with adherence. Results of univariate Logistic regression analysis showed that patients who used β-receptor blocking agents [OR＝1.65，95%CI（1.06，2.57），P＝0.027]， calcium channel blockers [OR＝2.13，95%CI（1.33， 3.42），P＝0.002] and agents acting on the renin-angiotensin system [OR＝2.04，95%CI（1.29，3.22），P＝0.002] had good medication adherence. CONCLUSIONS The medication adherence of hypertension patients needs to be improved. Hypertension patients with higher education level， lower average blood pressure level， complications and fixed-dose combination regimen and those who use agents acting on the renin-angiotensin system， calcium channel blockers and β-receptor blocking agents may have better medication adherence.

ObjectiveThe traditional Chinese medicine Strychnos nux-vomica L. (SN) has the clinical effect of reducing swelling and relieving pain; however, SN is toxic due to its alkaloid components. Little is known about the endogenous metabolic changes induced by SN toxicity in rats and their potential effects on the metabolic dysregulation of intestinal microbiota. Therefore, toxicological investigation of SN is of great significance to its safety assessment. In this study, the toxic mechanisms of SN were explored using a combination of metabonomics and 16S rRNA gene sequencing. MethodsThe toxic dose, intensity, and target organ of SN were determined in rats using acute, cumulative, and subacute toxicity tests. UHPLC-MS was used to analyze the serum, liver, and renal samples of rats after intragastric SN administration. The decision tree and K Nearest Neighbor (KNN) model were established based on the bootstrap aggregation (bagging) algorithm to classify the omics data. After samples were extracted from rat feces, the high-throughput sequencing platform was used to analyze the 16S rRNA V3-V4 region of bacteria. ResultsThe bagging algorithm improved the accuracy of sample classification. Twelve biomarkers were identified, where their metabolic dysregulation may be responsible for SN toxicity in vivo. Several types of bacteria such as Bacteroidetes, Anaerostipes, Oscillospira and Bilophila, were demonstrated to be closely related to physiological indices of renal and liver function, indicating that SN-induced liver and kidney damage may be related to the disturbance of these intestinal bacteria. ConclusionThe toxicity mechanism of SN was revealed in vivo, which provides a scientific basis for the safe and rational clinical use of SN.

Pulmonary disease is one of the major threats to human health. However, the current clinical treatment drugs for lung diseases generally have problems such as low lung delivery efficiency, fast clearance rate and obvious toxic side effects. Recently, membrane biomimetic nanocarriers have attracted more and more attention. Due to their advantages of high targeting, long cycle time, good biocompatibility and strong immune escape ability, membrane biomimetic nanocarriers have become a major research hotspot in targeted therapy of lung diseases. In this review, we discuss the main preparation methods of membrane biomimetic nanoparticles, the characteristics of membrane biomimetic nanocarriers from different cell sources and their application in the targeted therapy of lung diseases. At the same time, according to the characteristics of different membranes, the shortcomings, current technical limitations and future prospects are discussed. This review is expected to provide references for the design of membrane biomimetic nanocarriers and their potential applications in the treatment of lung diseases.

Objective:To investigate the effects of methyltransferases like 3(METTL3)mediated m6A modification of double homology cassette A pseudogene8(DUXAP8)on the proliferation,migration and invasion of salivary adenoid cystic carcinoma SACC-LM cells and its potential molecular mechanisms.Methods:Whole-transcriptome sequencing showed that DUXAP8 was highly ex-pressed in SACC than in para-cancerous tissues(P＜0.05).The m6A modification sites on DUXAP8 were predicted using the SRAMP website,and the mRNA and protein expression of m6A-modified genes and the genes associated with the epithelial-mesen-chymal transition(EMT)was measured by qRT-PCR and Western blot,respectively.METTL3 and DUXAP8 was knocked down or overexpressed in SACC-LM cells,and the proliferation,migration,and invasion of the cells were assessed by CCK-8,scratch and Transwell assays.The correlation between METTL3 and DUXAP8 was evaluated using MeRIP-qPCR.Results:The expression of DUXAP8 in SACC tumor was higher than that in para-cancerous tissues(P＜0.05).Knockdown of DUXAP8 reduced proliferation,migration and invasion of SACC-LM cells,as well as the expression of EMT-related genes(P＜0.05).Multiple m6A modification sites of high confidence were found on DUXAP8.METTL3 was highly expressed in tumor tissues,more than other related genes(P＜0.05)and enzyme-encoding genes in SACC-LM cells(P＜0.05).METTL3 was found to function as a methyltransferase to regulate the expression of DUX-AP8,and downregulation of METTL3 inhibited prolifera-tion,migration and invasion of SACC-LM cells and partially reversed the promotion of these activities induced by DUX-AP8 overexpression(P＜0.05).Conclusion:METTL3-me-diated m6A modification upregulated DUXAP8 expression,which promotes the proliferation,migration and invasion of SACC cells.

Objective To investigate the relationship between serum thrombin-antithrombin Ⅲ complex(TAT)and soluble fms-like tyrosine kinase-1(sFlt-1)levels and the progression and prognosis of sepsis pa-tients.Methods A total of 117 patients with sepsis admitted to the hospital from January 2021 to May 2023 were selected as the observation group,and 42 healthy volunteers in the hospital during the same period were selected as the control group.Patients with sepsis were divided into ordinary sepsis group(60 cases)and sep-tic shock group(57 cases).The observation group was divided into death group and survival group according to the prognosis after 90 days of treatment.Serum TAT and sFlt-1 levels were detected by enzyme-linked im-munosorbent assay.Logistic regression was used to analyze the death influencing factors of sepsis patients,and a prognostic prediction model of sepsis patients based on TAT and sFlt-1 was established.The predictive value of receiver operating characteristics(ROC)curve analysis indexes for the death of sepsis patients was evalua-ted.Results The levels of TAT[(12.59±5.35)ng/mL]and sFlt-1[(28.58±4.05)ng/mL]in the observa-tion group were higher than those in the control group[(2.65±0.88)ng/mL and(16.50±3.60)ng/mL,re-spectively].The difference was statistically significant(t=19.386,17.065,P＜0.001).The serum TAT[(15.09±4.99)ng/mL]and sFlt-1[(30.45±3.30)ng/mL]levels in septic shock group were higher than those in ordinary sepsis group[(10.22±4.57)ng/mL and(26.81±3.92)ng/mL,respectively].The differ-ence was statistically significant(t=5.503,5.429,P＜0.001).The proportion of septic shock,sequential or-gan failure assessment(SOFA)score,acute physiological and chronic health evaluation Ⅱ(APACHE Ⅱ)score,blood lactate,procalcitonin,TAT and sFlt-1 levels in the death group were higher than those in the sur-vival group,with statistical significance(P＜0.05).Sepsis shock,increased SOFA score,increased APACHEⅡ score and increased blood lactic acid,TAT and sFlt-1 were independent risk factors for death in sepsis pa-tients(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of the predictive model for predicting death in sepsis patients was 0.947,which was higher than the AUC predicted by disease degree,SOFA score,APACHE Ⅱ score,blood lactic acid,TAT,and sFlt-1 alone(Z=6.525,4.414,4.835,3.787,3.956,3.507,P＜0.001).Conclusion The increase of serum TAT and sFlt-1 levels in patients with sepsis is closely related to disease progression and poor prognosis,and the prediction model established based on TAT and sFlt-1 has high predictive value for the death of patients with sepsis.